4.6 Article

Lack of Activation of Mitophagy during Endurance Exercise in Human

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MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
卷 49, 期 8, 页码 1552-1561

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LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1249/MSS.0000000000001256

关键词

BNIP3; CYCLING; DRP1; FASTING; MITOCHONDRIA; PGC1A

资金

  1. Fonds de la Recherche Scientifique (Universite catholique de Louvain, UCL)

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Purpose: This study aimed to determine whether fission and mitophagy are activated by acute endurance exercise in human skeletal muscle and to investigate if this activation is dependent upon the nutritional state. Methods: Trained athletes (n = 7) cycled for 2 h at 70% (V)over dotO(2peak) in a fed or fasted state. Vastus lateralis muscle biopsies were obtained at baseline, before, immediately after, and 1 h after exercise. Protein and mRNA markers for mitophagy, mitochondrial biogenesis, fission, and fusion were analyzed using quantitative real-time polymerase chain reaction and Western blot. Results: Fission, assessed by phospho-DRP1(Ser616) in the mitochondrial fraction, increased postexercise and 1 h postexercise only in the fed state. LC3bII and p62/SQSTM1 in the mitochondrial fraction were unchanged, whereas the LC3bII/LC3bI ratio was decreased only postexercise in the fasted state (P = 0.019), indicating a reduced mitophagy. Genes implicated in fission and mitophagy, such as Drp1, Bnip3, and Bnip3L, and proteins involved in fission (Fis1) or mitophagy (BNIP3) were all more expressed after exercise in the fed state (P < 0.05). As expected, the mRNA levels of PGC1 alpha, Tfam, and Hsp60, all markers of mitogenesis, were increased after endurance exercise, but to a larger extent in the fed than that in the fasted state. Conclusion: The present study provides the very first evidence that mitophagy is not activated during and early after high-intensity endurance exercise in human, whatever the nutritional state, despite a selective activation of fission in the fed state. However, when nutrient availability is optimal, muscle cells seem capable of preparing mitochondria for lysosomal degradation. Thus, we may not exclude an activation of mitophagy at a later stage after exercise.

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